全文获取类型
收费全文 | 1010篇 |
免费 | 84篇 |
出版年
2023年 | 1篇 |
2022年 | 7篇 |
2021年 | 20篇 |
2020年 | 5篇 |
2019年 | 14篇 |
2018年 | 27篇 |
2017年 | 21篇 |
2016年 | 38篇 |
2015年 | 55篇 |
2014年 | 54篇 |
2013年 | 93篇 |
2012年 | 74篇 |
2011年 | 86篇 |
2010年 | 63篇 |
2009年 | 54篇 |
2008年 | 59篇 |
2007年 | 67篇 |
2006年 | 64篇 |
2005年 | 54篇 |
2004年 | 32篇 |
2003年 | 46篇 |
2002年 | 50篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1996年 | 2篇 |
1995年 | 8篇 |
1994年 | 11篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有1094条查询结果,搜索用时 171 毫秒
91.
Cinzia Comino Sergio Lanteri Ezio Portis Alberto Acquadro Annalisa Romani Alain Hehn Romain Larbat Frédéric Bourgaud 《BMC plant biology》2007,7(1):14
Background
Cynara cardunculus L. is an edible plant of pharmaceutical interest, in particular with respect to the polyphenolic content of its leaves. It includes three taxa: globe artichoke, cultivated cardoon, and wild cardoon. The dominating phenolics are the di-caffeoylquinic acids (such as cynarin), which are largely restricted to Cynara species, along with their precursor, chlorogenic acid (CGA). The scope of this study is to better understand CGA synthesis in this plant. 相似文献92.
Francesca Ghirga Federica Aiello Sara Toscano Cinzia Ingallina Mariangela Siler Danilo Cucchi Agnese Po Evelina Miele Davide D'Amico Gianluca Canettieri Enrico De Smaele Elisabetta Ferretti Isabella Screpanti Gloria Uccello Barretta Maurizio Botta Bruno Botta Alberto Gulino Lucia Di Marcotullio 《The EMBO journal》2015,34(2):200-217
93.
94.
Emanuela Dazzo Manuela Fanciulli Elena Serioli Giovanni Minervini Patrizia Pulitano Simona Binelli Carlo Di Bonaventura Concetta Luisi Elena Pasini Salvatore Striano Pasquale Striano Giangennaro Coppola Angela Chiavegato Slobodanka Radovic Alessandro Spadotto Sergio Uzzau Angela La Neve Anna Teresa Giallonardo Oriano Mecarelli Silvio C.E. Tosatto Ruth Ottman Roberto Michelucci Carlo Nobile 《American journal of human genetics》2015,96(6):992-1000
Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic epilepsy syndrome clinically characterized by focal seizures with prominent auditory symptoms. ADLTE is genetically heterogeneous, and mutations in LGI1 account for fewer than 50% of affected families. Here, we report the identification of causal mutations in reelin (RELN) in seven ADLTE-affected families without LGI1 mutations. We initially investigated 13 ADLTE-affected families by performing SNP-array linkage analysis and whole-exome sequencing and identified three heterozygous missense mutations co-segregating with the syndrome. Subsequent analysis of 15 small ADLTE-affected families revealed four additional missense mutations. 3D modeling predicted that all mutations have structural effects on protein-domain folding. Overall, RELN mutations occurred in 7/40 (17.5%) ADLTE-affected families. RELN encodes a secreted protein, Reelin, which has important functions in both the developing and adult brain and is also found in the blood serum. We show that ADLTE-related mutations significantly decrease serum levels of Reelin, suggesting an inhibitory effect of mutations on protein secretion. We also show that Reelin and LGI1 co-localize in a subset of rat brain neurons, supporting an involvement of both proteins in a common molecular pathway underlying ADLTE. Homozygous RELN mutations are known to cause lissencephaly with cerebellar hypoplasia. Our findings extend the spectrum of neurological disorders associated with RELN mutations and establish a link between RELN and LGI1, which play key regulatory roles in both the developing and adult brain. 相似文献
95.
96.
97.
98.
The peculiar heme pocket of the 2/2 hemoglobin of cold-adapted Pseudoalteromonas haloplanktis TAC125
Barry D. Howes Daniela Giordano Leonardo Boechi Roberta Russo Simona Mucciacciaro Chiara Ciaccio Federica Sinibaldi Maria Fittipaldi Marcelo A. Mart�� Dar��o A. Estrin Guido di Prisco Massimo Coletta Cinzia Verde Giulietta Smulevich 《Journal of biological inorganic chemistry》2011,16(2):299-311
The genome of the cold-adapted bacterium Pseudoalteromonas haloplanktis TAC125 contains multiple genes encoding three distinct monomeric hemoglobins exhibiting a 2/2 ??-helical fold. In the present work, one of these hemoglobins is studied by resonance Raman, electronic absorption and electronic paramagnetic resonance spectroscopies, kinetic measurements, and different bioinformatic approaches. It is the first cold-adapted bacterial hemoglobin to be characterized. The results indicate that this protein belongs to the 2/2 hemoglobin family, Group II, characterized by the presence of a tryptophanyl residue on the bottom of the heme distal pocket in position G8 and two tyrosyl residues (TyrCD1 and TyrB10). However, unlike other bacterial hemoglobins, the ferric state, in addition to the aquo hexacoordinated high-spin form, shows multiple hexacoordinated low-spin forms, where either TyrCD1 or TyrB10 can likely coordinate the iron. This is the first example in which both TyrCD1 and TyrB10 are proposed to be the residues that are alternatively involved in heme hexacoordination by endogenous ligands. 相似文献
99.
Vacca F D'Ambrosi N Nestola V Amadio S Giustizieri M Cucchiaroni ML Tozzi A Velluz MC Mercuri NB Volonté C 《Glycobiology》2011,21(5):634-643
N-Glycosylation affects the function of ion channels at the level of multisubunit assembly, protein trafficking, ligand binding and channel opening. Like the majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are glycosylated in their extracellular moiety. Here, we used site-directed mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of the role of N-glycans on protein stability, plasma membrane delivery, trimer formation and inward currents. We have found that in transiently transfected HEK293 cells, Asn(170) is apparently the most important site for receptor stability, since its mutation causes a primary loss in protein content and indirect failure in membrane expression, oligomeric association and inward current responses. Even stronger effects are obtained when mutating Thr(172) in the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable, since even their simultaneous mutation does not affect any tested receptor feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290) double mutant are instead almost unable to assemble into a functional trimeric structure. The main emerging finding is that the inability to assemble into trimers might account for the impaired function in P2X(3) mutants where residue Asn(170) is replaced. These results improve our knowledge about the role of N-glycosylation in proper folding and oligomeric association of P2X(3) receptor. 相似文献
100.
Simoni D Rondanin R Marchetti P Rullo C Baruchello R Grisolia G Barbato G Giovannini R Marchioro C Capelli AM Virginio C Bozzoli A Borea PA Merighi S Donati D 《Bioorganic & medicinal chemistry letters》2011,21(18):5423-5427
The introduction of the isoxazole ring as bioisosteric replacement of the acetyl group of anatoxin-a led to a new series of derivatives binding to nicotinic acetylcholine receptors. Bulkier substitutions than methyl at the 3 position of isoxazole were shown to be detrimental for the activity. The binding potency of the most interesting compounds with α1, α7 and α3β4 receptor subtypes, was, anyway, only at micromolar level. Moreover, differently from known derivatives with pyridine, isoxazole condensed to azabicyclo ring led to no activity. 相似文献